CAMBRIDGE, Mass.--(BUSINESS WIRE)--Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced the initiation of the Phase 2 EMBRAZE proof-of-concept trial, designed to assess the safety and efficacy of apitegromab, a highly selective myostatin inhibitor, to preserve lean muscle mass in individuals living with obesity and on background therapy of a GLP-1 receptor agonist (GLP-1 RA).

马萨诸塞州剑桥市。-（商业新闻短讯）--Scholar Rock（纳斯达克：SRRK）是一家晚期生物制药公司，专注于推进脊髓性肌萎缩症（SMA），心脏代谢紊乱和其他蛋白质生长因子发挥基础作用的严重疾病的创新治疗，今天宣布启动2期EMBRAZE概念验证试验，旨在评估阿匹曲单抗（一种高选择性肌肉生长抑制素抑制剂）的安全性和有效性，以保持肥胖患者的瘦肌肉质量，并对GLP-1受体激动剂（GLP-1 RA）进行背景治疗。

The results from this trial will inform the development of SRK-439, a novel investigational selective myostatin inhibitor optimized for the treatment of cardiometabolic disorders, including obesity..

该试验的结果将为SRK-439的开发提供信息，SRK-439是一种新型的研究性选择性肌肉生长抑制素抑制剂，可用于治疗包括肥胖在内的心脏代谢紊乱。。

The Company also announced new preclinical data from a head-to-head comparison of SRK-439 and an anti-activin receptor II (anti-ActRII) antibody, which demonstrate SRK-439’s potential as best in class in preserving lean mass in patients on GLP-1 RAs. This data will be presented by Mo Qatanani, Ph.D., Chief Scientific Officer, at Scholar Rock’s Investor Event, which begins today at 8:30 a.m.

该公司还宣布了SRK-439和抗激活素受体II（抗ActRII）抗体的头对头比较的新临床前数据，这表明SRK-439在GLP-1 RAs患者中保持瘦体重方面具有最佳潜力。这些数据将由首席科学官莫·卡塔纳尼博士在学者洛克的投资者活动上提交，该活动将于今天上午8:30开始。

ET and is being held in New York City..

正在纽约举行。。

“We are thrilled to have initiated the EMBRAZE clinical trial ahead of schedule and to share new data from our SRK-439 program, which we believe further support our hypothesis that selective latent myostatin inhibition has advantages over less selective approaches to safely and effectively maintain lean muscle mass,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer at Scholar Rock.

Scholar Rock总裁兼首席执行官Jay Backstrom医学博士说：“我们很高兴提前启动了EMBRAZE临床试验，并分享了SRK-439项目的新数据，我们认为这进一步支持了我们的假设，即选择性潜伏性肌生长抑制素抑制比选择性较低的方法更能安全有效地维持瘦肌肉质量。”。

“Selectivity is key in mitigating potential safety concerns for this patient population and we look forward to sharing additional preclinical data at the American Diabetes Association 84th Scientific Sessions in June to support the best-in-class potential of SRK-439.”.

“选择性是减轻该患者群体潜在安全问题的关键，我们期待着在6月的美国糖尿病协会第84届科学会议上分享更多的临床前数据，以支持SRK-439的最佳潜力。”。

New SRK-439 Data

新SRK-439数据

For the head-to-head preclinical research study, the Company generated and tested an anti-ActRII antibody (a murine equivalent of bimagrumab), along with a murine equivalent of SRK-439 in a weight-stable diet induced obesity (DIO) mouse model. Mice were given either semaglutide (0.04mg/kg, daily) with an IgG control antibody (weekly, 20mg/kg) or semaglutide (0.04mg/kg, daily) in combination with weekly injections of either SRK-439 (0.3-10mg/kg) or of the anti-ActRII antibody (0.3-20mg/kg).

对于头对头的临床前研究，该公司在体重稳定饮食诱导的肥胖（DIO）小鼠模型中产生并测试了抗ActRII抗体（相当于bimagrumab的鼠类）以及相当于SRK-439的鼠类。给予小鼠semaglutide（0.04mg/kg，每日）和IgG对照抗体（每周20mg/kg）或semaglutide（0.04mg/kg，每日），并每周注射SRK-439（0.3-10mg/kg）或抗ActRII抗体（0.3-20mg/kg）。

Quantitative nuclear magnetic resonance (qNMR) was used to analyze change in lean mass after four weeks of treatment..

定量核磁共振（qNMR）用于分析治疗四周后瘦体重的变化。。

Lean mass differences were significant in all doses of SRK-439 tested, supporting the hypothesis that SRK-439 could be an important therapy to aid in lean mass preservation and is suitable for subcutaneous dosing in a population of adults with obesity.

在所有测试剂量的SRK-439中，瘦体重差异均显着，这支持了以下假设：SRK-439可能是帮助瘦体重保存的重要疗法，适用于肥胖成年人的皮下给药。

SRK-439 attenuated the GLP-1 RA-driven lean mass loss in combination with semaglutide at a dose as low as 0.3 mg/kg (8.3% lean mass loss from baseline).

SRK-439与semaglutide联合使用可减轻GLP-1 RA驱动的瘦体重损失，剂量低至0.3 mg/kg（比基线瘦体重损失8.3%）。

Maximal effects observed at all doses over 1 mg/kg (4.2% lean mass loss from baseline at 10mg/kg), as compared to an IgG control + semaglutide (14.1% lean mass loss from baseline).

与IgG对照+semaglutide（从基线减少14.1%）相比，在超过1 mg/kg的所有剂量下观察到的最大效应（在10mg/kg时从基线减少4.2%的瘦质量）。

Superiority to anti-ActRII antibody was shown in all equivalent doses tested:

在所有测试的等效剂量中均显示出对抗ActRII抗体的优越性：

3 mg/kg: -4.7% SRK-439 vs. -12.0% for anti-ActRII

3 mg/kg：-4.7%的SRK-439与-12.0%的抗ActRII

1 mg/kg: -5.0% SRK-439 vs. -12.6% for anti-ActRII

1 mg/kg：-5.0%SRK-439与-12.6%抗ActRII

0.3 mg/kg: -8.3% SRK-439 vs. -15.4% for anti-ActRII

0.3 mg/kg：-8.3%SRK-439与-15.4%抗ActRII

Equivalent lean mass preservation was seen at the highest dose tested for both drugs; 10 mg/kg SRK-439 (-4.2%) and 20 mg/kg anti-ActRII (-4.3%).

在两种药物测试的最高剂量下观察到等效的瘦质量保存；10 mg/kg SRK-439（-4.2%）和20 mg/kg抗ActRII（-4.3%）。

“The data from this head-to-head comparison show that selectively inhibiting myostatin alone is sufficient to preserve lean mass on a background of GLP-1 RA, in preclinical models. Combined with the positive data observed at low doses of SRK-439, we believe that our selective myostatin approach is the right potential solution to preserve lean muscle mass while avoiding the potential off-target effects observed in less selective programs for this indication.

“这种头对头比较的数据表明，在临床前模型中，单独选择性抑制肌肉生长抑制素足以在GLP-1 RA的背景下保持瘦体重。结合低剂量SRK-439观察到的阳性数据，我们认为我们的选择性肌肉生长抑制素方法是保持瘦肌肉质量的正确潜在解决方案，同时避免了在这种适应症的选择性较低的程序中观察到的潜在脱靶效应。

We view this as strong evidence that SRK-439 could have a more favorable benefit/risk profile,” said Mo Qatanani, Ph.D., Chief Scientific Officer at Scholar Rock..

我们认为这是SRK-439可能具有更有利的收益/风险概况的有力证据，”Scholar Rock首席科学官Mo Qatanani博士说。。

Phase 2 EMBRAZE Trial Design

第二阶段EMBRAZE试验设计

Scholar Rock announced in January that the U.S. Food and Drug Administration cleared the Company’s Investigational New Drug (IND) application for EMBRAZE, a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide).

Scholar Rock于1月宣布，美国食品和药物管理局（FDA）批准了该公司针对EMBRAZE的研究性新药（IND）申请，EMBRAZE是一项随机、双盲、安慰剂对照的2期概念验证试验，旨在评估阿哌曲单抗在体重指数（BMI）>27（超重）或BMI>30（肥胖）且服用GLP-1 RA（替利帕肽或塞马鲁肽）的成年人中的疗效、安全性和药代动力学。

The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes..

EMBRAZE的目标招募对象是100名年龄在18-65岁之间的超重或肥胖且无糖尿病的受试者。。

As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry.

作为研究设计的一部分，治疗期为24周，所有受试者将接受GLP-1 RA。此外，在24周的治疗期间，所有受试者将以1:1的比例随机接受apitegromab或安慰剂，每四周静脉（IV）输注一次。主要终点是通过双能X射线吸收测定法评估的瘦体重从第24周的基线变化。

Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function..

次要终点包括额外的减肥措施，安全性和耐受性以及药代动力学结果。第24周和第32周的探索性终点包括心脏代谢参数（例如HbA1c），身体成分和身体机能。。

Primary data from EMBRAZE are expected in mid-2025 and will inform Scholar Rock’s development of SRK-439 towards an anticipated IND filing in 2025.

EMBRAZE的主要数据预计将在2025年年中发布，并将为Scholar Rock的SRK-439开发提供信息，以实现2025年的IND申报。

The presentation from Scholar Rock’s Investor Day will be available in the Investors and Media section of Scholar Rock’s website. Live webcast of the event may be accessed by visiting the Investors & Media section of the Scholar Rock website at http://investors.scholarrock.com. An archived replay of the webcast will be available on the Company’s website for approximately 90 days following the presentations..

Scholar Rock投资者日的介绍将在Scholar Rock网站的投资者和媒体部分提供。可通过访问学者摇滚网站的投资者和媒体部分访问活动的在线直播，网址为http://investors.scholarrock.com.演示结束后约90天内，公司网站将提供网络广播的存档重播。。

About SRK-439

关于SRK-439

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity.

SRK-439是一种新型的临床前研究性肌生长抑制素抑制剂，对促肌生长抑制素和潜伏性肌生长抑制素具有较高的体外亲和力，并维持肌生长抑制素的特异性（即无GDF11或激活素-a结合），最初被开发用于治疗心脏代谢紊乱，包括肥胖。

Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency..

根据临床前数据，SRK-439有可能通过在减肥过程中保持瘦体重来支持更健康的体重管理。SRK-439的有效性和安全性尚未确定，并且SRK-439尚未被FDA或任何其他监管机构批准用于任何用途。。

About Apitegromab

关于Apitegromab

Apitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA).

Apitegromab是一种通过选择性结合骨骼肌中肌生长抑制素的前体和潜伏形式来抑制肌生长抑制素活化的研究性全人单克隆抗体。它是第一个在脊髓性肌萎缩症（SMA）中证明临床概念验证的肌肉靶向治疗候选者。

Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA.

肌肉生长抑制素是生长因子TGFβ超家族的成员，主要由骨骼肌细胞表达，其基因的缺失与包括人类在内的多种动物的肌肉质量和力量增加有关。Scholar Rock认为，阿匹曲单抗对肌肉生长抑制素的前体和潜在形式的高度选择性靶向可能会导致SMA患者运动功能的临床意义改善。

The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. The efficacy and safety of apitegromab have not been established and apitegromab has not been approved for any use by the FDA or any other regulatory agency..

美国食品和药物管理局（FDA）已授予快速通道，孤儿药和罕见儿科疾病名称，欧洲药品管理局（EMA）已授予apitegromab优先药物（PRIME）和孤儿药品名称，用于治疗SMA。阿替格玛的有效性和安全性尚未确定，阿替格玛尚未被FDA或任何其他监管机构批准用于任何用途。。

About Scholar Rock

关于学者岩

Scholar Rock is a biopharmaceutical company that discovers, develops, and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of the transforming growth factor beta (TGFβ) superfamily of cell proteins and named for the visual resemblance of a scholar rock to protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental.

Scholar Rock是一家生物制药公司，为严重疾病患者发现、开发和提供改变生活的疗法，这些患者的需求尚未得到满足。作为细胞蛋白转化生长因子β（TGFβ）超家族生物学的全球领导者，该公司以学者摇滚与蛋白质结构的视觉相似性而命名，临床阶段公司专注于推进蛋白质生长因子为基础的创新治疗。

Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role..

在过去的十年中，学者洛克（Scholar Rock）创建了一条管道，有可能提高神经肌肉疾病、心脏代谢紊乱、癌症和其他生长因子靶向药物可以发挥变革作用的疾病的护理标准。。

Scholar Rock is the only company to show clinical proof-of-concept for a muscle-targeted treatment in spinal muscular atrophy (SMA). This commitment to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity.

Scholar Rock是唯一一家为脊髓性肌萎缩症（SMA）的肌肉靶向治疗提供临床概念验证的公司。这种解锁根本不同的治疗方法的承诺是由专有平台的广泛应用所推动的，该平台开发了新型单克隆抗体，以非凡的选择性调节蛋白质生长因子。

By harnessing cutting-edge science in disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create new possibilities for patients. Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn..

学者洛克（Scholar Rock）每天都在利用传统疗法无法解决的疾病领域的尖端科学，为患者创造新的可能性。在ScholarRock.com了解更多有关我们的方法的信息，并关注@ScholarRock和LinkedIn。。